The invention relates to a nucleotide sequence which encodes the PRV-1 gene, to recombinant DNA which contains this nucleotide sequence, to vectors which contain the recombinant DNA and to cells which are transformed with these vectors, and also to a PRV-1 polypeptide, to antibodies against this polypeptide, to a process for detecting the PRV-1 polypeptide and to drugs which comprise the PRV-1 polypeptide or antibodies which are directed against the PRV-1 polypeptide.
Polycythaemia rubra vera (erythraemia), also termed polycythaemia vera or p. vera, is a malignant haematological disease in which there is an increased formation of erythroid, granulocytic and megakaryocytic cells. The disease is of clonal origin and arises as a result of the mutation of a single haematopoietic precursor cell. In Germany, the incidence of p. vera is from 4 to 6 per million inhabitants. If left untreated, the disease leads to death within 18 months. Treatment by means of blood-letting or chemotherapy extends the average survival time to more than 13 years.
P. vera is diagnosed by means of clinical criteria. The clinical picture includes headaches, pruritus, splenomegaly in two thirds of the patients, bleeding or thromboses, hypertension in a third of the patients, gout, which is brought about by an increase in the production of uric acid, and, in some cases, septic ulcers. The most important laboratory finding is an increase in the values for haemoglobin, haematocrit, erythrocyte count and total erythrocyte volume, and also a neutrophilic granulocytosis or thrombocytosis in many cases. Since, on the one hand, most of the criteria are rather diffuse and, on the other hand, not all the patients fulfil these criteria, it is frequently difficult to distinguish p. vera from other myeloproliferative diseases, such as chronic granulocytic leukaemia or essential thrombocytosis, and thereby confirm the diagnosis. To date, the molecular cause of p. vera is completely unknown. Since, however, p. vera takes a severe course if it is not treated, accurate diagnosis is important.
An object of the invention was therefore to find the molecular cause of polycythaemia rubra vera and to create the possibility of diagnosing it.
This object was achieved by isolating a gene which is expressed specifically in association with p. vera and not in healthy control individuals. This gene is designated the PRV-1 gene (polycythaemia rubra vera).
A similar nucleotide sequence is disclosed in International application WO 98/50552.